ethyl 3-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate | 1042441-75-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: ethyl 3-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate
• 英文别名: Thieno[2,3-b]pyridine-2-carboxylic acid, 3-bromo-4,6-dimethyl-, ethyl ester
• CAS: 1042441-75-7
• 化学式: C₁₂H₁₂BrNO₂S
• 分子量: 314.203
• InChiKey: HSYSBDULYCEOTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate 在 caesium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 25.08h， 生成 2,4-dimethylthieno[2,3-b:5,4-c']dipyridin-8-ol
  参考文献：
  名称：

  结构不同的三环 M4 正变构调节剂 (PAM) 化学型的发现——第 2 部分

  摘要：

  这封信详细介绍了我们为开发具有改进的药理特性的新型三环 M 4 PAM 支架所做的努力。这项努力涉及一种“回接”策略，以取代 3-amino-4,6-dimethylthieno[2,3- b ]pyridine-2-carboxamide 核心，从而发现了两个新的三环核心：7,9 -二甲基吡啶并[3',2':4,5]噻吩并[3,2-d]嘧啶核和2,4-二甲基噻吩并[2,3 - b :5,4-c']联吡啶核。两个三环核心都显示出对人类 M 4受体的低纳摩尔效力。

  DOI：

  10.1016/j.bmcl.2021.128416
• 作为产物：
  描述：

  2-氯-3-氰基-4,6-二甲基吡啶 在 亚硝酸特丁酯 、 potassium carbonate 、 copper(I) bromide 作用下， 以 乙醇 、 乙腈 、 叔丁醇 为溶剂， 反应 15.83h， 生成 ethyl 3-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate
  参考文献：
  名称：

  [EN] POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4
  [FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR MUSCARINIQUE DE L'ACÉTYLCHOLINE M4

  摘要：

  本文披露了硫代噻吡啶[2,3-b:5,4-c']二吡啶-8-胺和吡啶[4',3':4,5]硫代噻吡啶[2,3-c]吡啉-8-胺化合物，这些化合物可能作为胆碱能受体M4（mAChR M4）的阳性变构调节剂而有用。本文还披露了制备这些化合物的方法、包含这些化合物的药物组合物，以及利用这些化合物和组合物治疗与胆碱能受体功能障碍相关的神经和精神疾病的方法。

  公开号：

  WO2018085813A1

文献信息

• SPIRO-RING COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2128163A1

  公开（公告）日：2009-12-02

  The present invention aims to provide a compound having an acetyl-CoA carboxylase (ACC) inhibitory action, which is useful for the prophylaxis or treatment of obesity, diabetes, hypertension, hyperlipidemia, cardiac failure, diabetic complications, metabolic syndrome, sarcopenia, cancer and the like, and has superior efficacy. The present invention provides a compound represented by the formula (I): wherein R1 is a hydrogen atom or a substituent; ring P is an optionally substituted 6-membered nitrogen-containing aromatic heterocycle; ring Q is an optionally further substituted 5- to 7-membered nitrogen-containing non-aromatic heterocycle; and ring R is an optionally fused 5- to 7-membered non-aromatic ring, which is further optionally substituted, or a salt thereof.

  本发明旨在提供一种具有乙酰辅酶A羧化酶（ACC）抑制作用的化合物，该化合物对于预防或治疗肥胖、糖尿病、高血压、高脂血症、心力衰竭、糖尿病并发症、代谢综合征、肌少症、癌症等具有卓越疗效。 本发明提供一种由以下式（I）表示的化合物： 其中 R1是氢原子或取代基； 环P是可选择取代的含氮芳香杂环； 环Q是可选择进一步取代的5-至7-成员的含氮非芳香杂环；和 环R是可选择融合的5-至7-成员的非芳香环，进一步可选择取代， 或其盐。
• [EN] SUBSTITUTED THIENO[2,3-B]PYRIDINE-2-CARBOXAMIDE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4<br/>[FR] ANALOGUES DE THIÉNO[2,3-B]PYRIDINE-2-CARBOXAMIDE SUBSTITUÉS À UTILISER EN TANT QUE MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR MUSCARINIQUE DE L'ACÉTYLCHOLINE M4
  申请人：UNIV VANDERBILT

  公开号：WO2015027204A1

  公开（公告）日：2015-02-26

  In one aspect, the invention relates to substituted thieno[2,3-b]pyridine-2-carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及替代噻吩[2,3-b]吡啶-2-羧酰胺类似物，其衍生物和相关化合物，这些化合物可用作肌胆碱受体M4（mAChR M4）的正向别构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与肌胆碱受体功能障碍相关的神经系统和精神疾病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不限制本发明。
• SUBSTITUTED THIENO[2,3-B]PYRIDINE-2-CARBOXAMIDE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4
  申请人：Vanderbilt University

  公开号：US20160200733A1

  公开（公告）日：2016-07-14

  In one aspect, the invention relates to substituted thieno[2,3-b]pyridine-2-carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M 4 (mAChR M 4 ); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及替代噻吩[2,3-b]吡啶-2-羧酰胺类似物、其衍生物和相关化合物，其作为肌动蛋白乙酰胆碱受体M4（mAChR M4）的正向变构调节剂具有用途；制备这些化合物的合成方法；包含这些化合物的制药组合物；以及使用这些化合物和组合物治疗与肌动蛋白乙酰胆碱受体功能障碍相关的神经和精神障碍的方法。本摘要旨在作为搜索特定技术领域的扫描工具，不限制本发明。
• Positive allosteric modulators of the muscarinic acetylcholine receptor M4
  申请人：Vanderbilt University

  公开号：US10927126B2

  公开（公告）日：2021-02-23

  Disclosed herein are thieno[2,3-b:5,4-c′]dipyridin-8-amine and pyrido[4′,3′:4,5]thieno[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

  本文公开了噻吩并[2,3-b:5,4-c′]二吡啶-8-胺和吡啶并[4′,3′:4,5]噻吩并[2,3-c]哒嗪-8-胺化合物，它们可用作毒蕈碱乙酰胆碱受体 M4（mAChR M4）的正异位调节剂。本文还公开了制造这些化合物的方法、包含这些化合物的药物组合物，以及使用这些化合物和组合物治疗与毒蕈碱乙酰胆碱受体功能障碍相关的神经和精神疾病的方法。
• Novel M4 positive allosteric modulators derived from questioning the role and impact of a presumed intramolecular hydrogen-bonding motif in β-amino carboxamide-harboring ligands
  作者：Michael S. Poslusney、James M. Salovich、Michael R. Wood、Bruce J. Melancon、Katrina A. Bollinger、Vincent B. Luscombe、Alice L. Rodriguez、Darren W. Engers、Thomas M. Bridges、Colleen M. Niswender、P. Jeffrey Conn、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2018.12.039

  日期：2019.2

  This letter describes a focused exercise to explore the role of the beta-amino carboxamide moiety found in all of the first generation M-4 PAMs and question if the NH2 group served solely to stabilize an intramolecular hydrogen bond (IMHB) and enforce planarity. To address this issue (and to potentially find a substitute for the beta-amino carboxamide that engendered P-gp and contributed to solubility liabilities), we removed the NH2, generating des-amino congeners and surveyed other functional groups in the beta-position. These modifications led to weak M-4 PAMs with poor DMPK properties. Cyclization of the beta-amino carboxamide moiety by virtue of a pyrazole ring re-enforced the IMHB, led to potent (and patented) M-4 PAMs, many as potent as the classical bicyclic beta-amino carboxamide analogs, but with significant CYP1A2 inhibition. Overall, this exercise indicated that the beta-amino carboxamide moiety most likely facilitates an IMHB, and is essential for M(4)PAM activity within classical bicyclic M-4 PAM scaffolds.